Never Enough: The Neuroscience and Experience of Addiction

by Judith Grisel

an English traveler named Frederick Marryat noted in his diary that American practice was “if you meet, you drink; if you part, you drink; if you make acquaintance, you drink; if you close a bargain, you drink; they quarrel in their drink, and they make it up with a drink. They drink, because it is hot; they drink, because it is cold.”

True, at times life can be awful, disappointing, terrifying, or mind-numbingly tedious. But just the same, there is the frequent possibility of being overcome with joy, gratitude, or delight. In short, it is likely impossible to tamp down terror without also leveling pleasure. As Socrates noted, and many appreciate, sorrow and joy depend on each other; I prefer the roller coaster to the train.

addicts may be those who are especially charmed by the quality of carrots and immune to the beating of sticks, as any municipal court could attest.

Because beta-endorphin contributes to a sense of well-being by soothing stress and facilitating social affiliation, those of us with naturally low levels may experience less sense of safety and connection, even as children, on a day-to-day basis. That is, until John Barleycorn is invited to the party! Data such as these suggest that some of us are especially likely to find alcohol reinforcing because we can use it to medicate an innate opioid deficiency. Perhaps the “hole in my soul” I felt finally filled in my friend’s basement was nothing more than a flood of endorphins at last quenching destitute receptors.

A further increase in drinking is actually good for some. Worldwide annual revenue from alcohol sales is about $150 billion. Diageo and Anheuser-Busch InBev are two of the leading global producers and have net profit margins of around 25 percent as they invest more in marketing than they do in payroll. In its 2013 annual report, Anheuser-Busch InBev articulated its goal to “create new occasions to share our products with consumers.” This seems funny, because it obviously isn’t creating the occasion, but rather the excuse to use an occasion for drinking. These businesses are well aware of psychological learning principles as they work to associate contexts with alcohol, noting that “insights have enabled us to create and position products for specific moments of consumption: enjoying a game or music event with friends, shifting toward a more relaxed mood after work, celebrating at a party or sharing a meal.” Along similar lines, in 2014 the British Beer Alliance, a consortium of major British brewers, invested £10 million in the marketing campaign “There’s a Beer for That,” aiming to showcase “the variety of beer available in the UK and how these different styles fit perfectly a wide range of occasions.”

by the 1970s, Valium was the single most prescribed brand of medicine in the United States, used by about one in five women. It was also the cause of more emergency room visits than all illicit drugs combined. Though overdose from Valium is virtually impossible, withdrawal symptoms are anything but banal; combined with tolerance and craving, these drugs are highly addictive. Nonetheless, in 1980, 2.6 billion pills were dispensed, which is almost one hundred doses per person.1 Since then, minor modifications to the formulations have ensured a steady stream of patentable products, and use of these addictive drugs is higher than ever. In 2013, close to 6 percent of U.S. adults filled more than thirteen million prescriptions for sedative-hypnotics.

The popularity of barbiturates grew rapidly, and by the 1920s they were virtually the sole treatment for conditions benefiting from sedation. However, in 1960 Valium was introduced, initiating a second wave in this pharmacological revolution. All of these compounds are sedating in that they induce both muscular and psychic relaxation; “hypnotic” refers to their sleep-inducing properties. Because stress, anxiety, and insomnia are such common problems, it makes sense that these drugs have been popular since their introduction. Unfortunately, the problem with all the drugs that have been developed to treat these serious issues thus far is that with regular use they elicit an opponent process, therefore creating the state they were designed to remedy. The insomniac become sleepless. The anxious become wrecks.

Though hardly recreational in a classic sense, these drugs have tremendous appeal for many of us because feelings can be so darn uncomfortable. How nice just to float along in a perpetual twilight, somehow above the morass of anguish that comes with consciousness. Work was more tolerable, annoyances less irritating, ugliness, pain, and death less unbearable.

What’s in vogue in any era will mirror the social context. Anti-anxiety drugs (benzodiazepines) were especially popular before and during the “liberation movement,” as if the stress invoked by raising awareness created a bigger need for checking out (or the other way around: sedatives may help us avoid addressing social or personal injustice). Similarly, the opiate epidemic might reflect a reluctance to deal with suffering—in our own lives, but also in the collective as we slowly come to face our complicity in the world’s misery and twenty-four-hour news makes it ever less possible to escape tragedies big and small. Or we might speculate that the decline in the use of tranquilizers, caused mostly by negative press and pressure on doctors to reduce the number of prescriptions written, was related to the rise of alcohol use. It would be no wonder, because these drugs essentially represent alcohol in pill form. My point is, there will always be something available to assuage the need to escape the human experience.

Barbital was a wonder drug. The ability to sedate and promote sleep in clinical patients was no small feat. An Italian psychiatrist, Giuseppe Epifanio, was the first to report on this effect in an article published in 1915, though because it was during the war, and in Italian, it wasn’t widely appreciated. He wrote to describe the result of giving phenobarbital to a nineteen-year-old girl with resistant manic-depressive psychosis. Not only did she fall into a deep sleep, but she went into an extended remission. Eventually “sleep cures” consisting of prolonged sleep therapy caught on and during the 1920s were the only pharmacological treatment for psychosis. They were also used for autism, delirium tremens, and morphine withdrawal.

Phenobarbital is currently the most widely prescribed antiepileptic drug in the world, aptly dubbed “king of the barbiturates.”

The crowning nefarious use of barbiturates is state-administered murder. Thirty-three U.S. states, plus the U.S. military and the federal government, authorize use of the death penalty. The preferred method is by lethal injection, and since 1976, 1,483 executions have been carried out using this method. A cocktail of three drugs is employed: the barbiturate sodium thiopental is used to induce unconsciousness, another to paralyze muscles, and a third to stop the heartbeat. The U.S. manufacturer of sodium thiopental stopped making the drug after its production moved to Italy and the government there threatened to ban its export unless the company could ensure it was not being used for this purpose. The shortage has somewhat slowed the pace of executions.

People’s individual differences in a drug’s rewarding effects, as well as the development of tolerance or dependence, have been associated with structural differences in the GABAA receptor.4 For example, whether or not you are able to drink others under the table, or are known as a “lightweight,” has been attributed to the particular makeup of subunits. Structural differences may also confer individual variation in pain sensitivity, anxiety, premenstrual or postpartum depression, diagnosis on the autism spectrum, and need for sleep, among others.

The demand for benzos is higher than ever. Excessive anxiety is estimated to be the sixth leading cause of disability across the globe.5 Anxiety differs from fear in that the latter is an emotional response to a clear and current danger, as opposed to apprehension about possible future events or unfocused or irrational worry. There are many ways anxiety disorders are expressed, including panic disorder, phobias, obsessive-compulsive disorder, or PTSD (post-traumatic stress disorder). Anxiety disorders are also linked to depression; these are sometimes thought of as two sides of the same underlying issue(s). Anxiety disorders tend to begin early in life and follow a recurrent, intermittent course, exacting costs on life satisfaction, income, education, and relationships. Anxiety is also a major contributor to suicide. On the other hand, at moderate levels anxiety actually improves performance by boosting our energy level and helping us work or focus longer and harder. And anxiety may be an important survival tool because without it we wouldn’t be as likely to stay safe. Like many mental disorders, it is thought to reflect an excess of some healthy tendency; neither too little nor too much anxiety is ideal, and we can tell if it is too much when it impedes a person’s living to her fullest potential.

Though they might have begun taking anxiolytics to help them cope with a specific event or stressor, adaptation to these drugs is robust and inevitable, guaranteeing a particularly anxiety-ridden day if one skips a dose. The same is true for those who regularly take any benzodiazepine to help with insomnia. The benefits dwindle over time, at least for patients, if not for pharmaceutical companies. Again, it’s a bit of a double bind because, like anxiety, insomnia is a major problem. Around a quarter of adults report insomnia symptoms, and a chronic lack of sleep contributes to increased risk of cardiovascular and metabolic disease (including heart attacks and obesity), cancer, psychiatric illness including substance abuse, and impaired cognition and behavior. In the United States, about two million drivers fall asleep at the wheel every week, and drowsy drivers crash every twenty-five seconds. So obviously a lack of good sleep is problematic. It would be terrific to be able to pop a pill and experience a deep, restful sleep whenever we wanted. Unfortunately, unless this is a rare practice, the opponent process makes it impossible. On the first night, the drug does work like a charm, quickly and effectively transporting one to the land of nod. But like all drugs that produce their effects by altering activity of the brain, the honeymoon period doesn’t last long.

The drug historian Nicolas Rasmussen points out that “the history of tranquilizers is an endless cycle of ‘product innovation,’ to put it neutrally, with each one pretending to have no side effects and be non-addictive. Then, when these properties are discovered, the drug companies just [promote a] new one.”9 From a neuroscience perspective, the robust and unavoidable b process universally elicited by any GABAA agonist makes these drugs unsuitable for regular use. It might be a good time to ask, given our long and ardent relationship with this class of drugs despite their substantial liabilities, whether there is a better way to help those suffering with insomnia or anxiety. Or even to wonder how these conditions are so common as to be statistically normal—indeed they afflict at least one in three adults in the United States—yet still are considered abnormal behaviors. One possibility is that some people are more sensitive, or more exposed, than others to environmental factors that contribute to these conditions. For example, a growing scientific consensus suggests that overexposure to light such as that emanating from our beloved screens disrupts circadian rhythms to adversely affect a range of health outcomes including mood and sleep.10 Twenty years into a second century of abuse of this class of mainly prescription drugs, it might be time to look for alternative ways of coping—especially ones that don’t make the problem worse.

The stimulants methylphenidate (Ritalin) and amphetamine (Adderall) have been effectively used to treat attention deficit hyperactivity disorder (ADHD) for almost sixty years. ADHD diagnoses are common: in the United States, about 12 percent of children over age four have a diagnosis for an attention deficit disorder, and most of these, about four million, are treated with stimulants each day.1 The difference between those with ADHD diagnoses and those without is quantitative: for those with the disorder, drug treatment brings their cognition within normal range. Nonetheless, the high rates of use of these drugs in clinical populations, as well as by many in the normal range looking for enhancement rather than treatment, have led to concerns about possible long-term effects, and especially to the fear that the treatment may increase the risk for subsequently developing addiction. Given what we know about adaptation, it seems especially plausible because these drugs increase dopamine levels throughout the brain, including in the nucleus accumbens. In general, though, the research suggests that when these drugs are used as prescribed for ADHD, chronic exposure to them does not have lasting effects on behavior or cognition.2